Disease-Related and All-Cause Health Care Costs of Elderly Patients With Gout

BACKGROUND: Gout is a common cause of inflammatory arthritis in the United States, and its prevalence has increased in recent decades, especially among older adults. Older adults with gout are of particular interest because they tend to experience higher rates of tophi, an advanced stage of gout, than do younger patients. OBJECTIVES: For older adults with gout to (1) assess health care utilization and costs from a third-party payer perspective; (2) evaluate health care costs related to tophi; and (3) explore the relationship between elevated serum uric acid (UA) level, an indicator of disease control, and health care utilization. METHODS: Data were extracted from the Integrated Healthcare Information Services (IHCIS) claims database (1999-2005), which includes approximately 40 private health plans in the United States for approximately 13 million beneficiaries, about 4% of whom are aged 65 years or older. Patients were included in the study if they: (1) had 2 diagnoses of gout (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code of 274.xx) on separate medical claims or 1 gout diagnosis plus at least 1 gout-related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or sulfinpyrazone); (2) were at least 65 years old at the first diagnosis date (study index date); and (3) had 1 year of continuous eligibility both before and after the study index date. A comparison sample of elderly members without gout was selected using a 1:1 match to gout patients based on age, gender, and geographic region. Individuals in the comparison group also had 1 year of continuous eligibility both before and after the study index date, defined as the same index date as the respective matched gout patient. Patients with possible tophi were identified from at least 1 medical claim with an ICD-9-CM code 274.8x (274.81=gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear; 274.89 = gout with other specified manifestations) during the 12-month study period following the study index date. Additionally, a subgroup of gout patients with at least 1 serum UA measure was selected. Patients were divided into 3 groups according to their serum UA level on the earliest test date (serum UA index date): low (less than 6 mg per dL), moderate-high (6-8.99 mg per dL), and very high (e 9 mg per dL). Health care utilization was categorized into inpatient services, outpatient services, emergency room services, other medical services, and use of prescription drugs. Medical services were classified by the place of service indicated in the claim. Medical services costs and pharmacy costs were defined as the amount paid to the provider plus member cost share (e.g., deductible, copayment). Two types of costs were assessed in the analysis: total all-cause health care costs and gout-related costs, defined as costs associated with a claim with a primary or secondary diagnosis of gout (ICD-9-CM code 274.xx). Differences in total all-cause health care costs were calculated by comparing (1) gout patients and gout-free members during the 12-month period following the study index date; (2) gout patients with and without tophi during the 12-month period following the study index date; and (3) gout patients across the 3 serum UA categories during the 12-month period following the serum UA index date. Multivariate regression analyses were used to control for patients' baseline demographics, prior comorbidities indicated by the Deyo-Charlson Comorbidity Index, and number of medications used during the 12 months prior to the study index date. RESULTS: Over the 7 years of claims data through 2005, there were 11,935 gout patients aged 65 years or older. The sample had an average age of 71.4 years and was predominantly male (73.5%). In the 12 months following the study index date, the mean unadjusted per-patient gout related health care cost was $876 (standard deviation $3,373) in 2005 dollars, 5.9% of the total all-cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted total 12-month all-cause health care cost for the gout-free members was $9,219 (SD $20,186). After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients and gout-free members was $3,038 (P less than 0.001). A diagnosis suggesting possible tophi was found in 2.0% (n = 240) of gout patients in the sample. After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients with and without tophi was $5,501 (P less than 0.001), and the difference in total adjusted 12-month gout-related costs between patients with and without tophi was $1,710 (P less than 0.001). Among the 2,237 (18.7%) patients with at least 1 serum UA measure, 28.3% had a low serum UA level, 52.4% had a moderate-high serum UA level, and 19.3% had a very high serum UA level. For patients with low, moderate-high, and very high serum UA levels, regression-adjusted gout-related costs in the 12 months following the serum UA index date represented, respectively, 2.9%, 2.7%, and 3.9% of total regression-adjusted health care costs. The group with a very high serum UA level had significantly higher regression-adjusted total 12-month all-cause health care costs and gout-related costs compared with those with a low serum UA level ($3,103 and $276 higher, respectively). CONCLUSIONS: Elderly patients with a diagnosis of gout have higher all-cause health care utilization and costs compared with matched elderly patients without a diagnosis of gout. Gout-related costs represent about 6% of total health care costs in elderly patients with gout. Very high serum UA levels (i.e., = 9 mg per dL) and diagnoses suggesting possible tophi are associated with increased utilization and costs in elderly gout patients.

OBJECTIVE: For older adults with gout to (1) assess health care utilization and costs from a third-party payer perspective; (2) evaluate health care costs related to tophi; and (3) explore the relationship between elevated serum uric acid (UA) level, an indicator of disease control, and health care utilization.
METHODS: Data were extracted from the Integrated Healthcare Information Services (IHCIS) claims database (1999)(2000)(2001)(2002)(2003)(2004)(2005), which includes approximately 40 private health plans in the United States for approximately 13 million beneficiaries, about 4% of whom are aged 65 years or older. Patients were included in the study if they: (1) had 2 diagnoses of gout (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code of 274.xx) on separate medical claims or 1 gout diagnosis plus at least 1 gout-related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or sulfinpyrazone); (2) were at least 65 years old at the first diagnosis date (study index date); and (3) had 1 year of continuous eligibility both before and after the study index date. A comparison sample of elderly members without gout was selected using a 1:1 match to gout patients based on age, gender, and geographic region. Individuals in the comparison group also had 1 year of continuous eligibility both before and after the study index date, defined as the same index date as the respective matched gout patient. Patients with possible tophi were identified from at least 1 medical claim with an ICD-9-CM code 274.8x (274.81=gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear; 274.89 = gout with other specified manifestations) during the 12-month study period following the study index date. Additionally, a subgroup of gout patients with at least 1 serum UA measure was selected. Patients were divided into 3 groups according to their serum UA level on the earliest test date (serum UA index date): low (< 6 mg per dL), moderate-high (6-8.99 mg per dL), and very high (≥ 9 mg per dL). Health care utilization was categorized into inpatient services, outpatient services, emergency room services, other medical services, and use of prescription drugs. Medical services were classified by the place of service indicated in the claim. Medical services costs and pharmacy costs were defined as the amount paid to the provider plus member cost share (e.g., deductible, copayment). Two types of costs were assessed in the analysis: total all-cause health care costs and gout-related costs, defined as costs associated with a claim with a primary or secondary diagnosis of gout (ICD-9-CM code 274.xx). Differences in total all-cause health care costs were calculated by comparing (1) gout patients and gout-free members during the 12-month period following the study index date; (2) gout patients with and without tophi during the 12-month period following the study index date; and (3) gout patients across the 3 serum UA categories during the 12-month period following the serum UA index date. Multivariate regression analyses were used to control for patients' baseline demographics, prior comorbidities indicated by the Deyo-Charlson Comorbidity Index, and number of medications used during the 12 months prior to the study index date. RESULTS: Over the 7 years of claims data through 2005, there were 11,935 gout patients aged 65 years or older. The sample had an average age of 71.4 years and was predominantly male (73.5%). In the 12 months following the study index date, the mean unadjusted per-patient goutrelated health care cost was $876 (standard deviation $3,373) in 2005 dollars, 5.9% of the total all-cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted total 12-month all-cause health care cost for the gout-free members was $9,219 (SD $20,186). After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients and gout-free members was $3,038 (P < 0.001). A diagnosis suggesting possible tophi was found in 2.0% (n = 240) of gout patients in the sample. After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients with and without tophi was $5,501 (P < 0.001), and the difference in total adjusted 12-month gout-related costs between patients with and without tophi was $1,710 (P < 0.001). Among the 2,237 (18.7%) patients with at least 1 serum UA measure, 28.3% had a low serum UA level, 52.4% had a moderate-high serum UA level, and 19.3% had a very high serum UA level. For patients with low, moderate-high, and very high serum UA levels, regression-adjusted gout-related costs in the 12 months following the serum UA index date represented, respectively, 2.9%, 2.7%, and 3.9% of total regression-adjusted health care costs. The group with a very high serum UA level had significantly higher regression-adjusted total 12-month all-cause health care costs and gout-related costs compared with those with a low serum UA level ($3,103 and $276 higher, respectively).
• The physiological pathway between hyperuricemia and prevalence of gout is well understood. From an epidemiological perspective, however, the relationship between serum UA and cost of gout has not been well established, especially among older adults. • The existing pharmacoeconomics literature shows that the costs of gout treatment may be substantial, although no cost study to our knowledge has focused specifically on the older adult population.

R E S E A R C H
G out is a disease caused by the deposition of monosodium urate crystals on the articular cartilage of joints and tissues like tendons. Gout currently affects approximately 5.1 million people in the United States 1 and is the most common cause of inflammatory arthritis in men. 2,3 In terms of prevalence, gout affects between 0.4% and 4.4% of the population, depending on age and gender. 4 The prevalence of gout has risen in recent decades. 2,[5][6][7][8][9] For example, the incidence rate of primary gout in the United States increased 2-fold between the mid-1970s and the mid-1990s. 5 These increases can be explained in part by changes in the prevalence of several risk factors for gout, such as obesity, increasing longevity, and hyperlipidemia. Other important risk factors include renal insufficiency, alcohol abuse, use of diuretics in hypertension and congestive cardiac failure, and prophylactic low-dose aspirin. [2][3][4]10,11 Despite the high prevalence of gout, the economic burden of the disease has not been well studied. The literature that exists, however, indicates that the cost of gout treatment may be substantial. Kim et al. estimated that annual gout-related treatment costs for new acute cases in the United States are approximately $27 million. 2 Brook et al. found that the total annual employer health benefit costs per person (i.e., medical and prescription claims, sick and disability leave, and workers' compensation) are $3,165 higher for employees with gout compared with those without gout. 12 One reason gout can be costly is that the disease can evolve into a phase of chronic tophaceous gout, characterized by tophi forming around the joints and subcutaneous tissues. 2,10 Tophi are chalky deposits of sodium urate, which can produce persistent pain and nerve compression syndrome, cause ulceration of the skin, and lead to joint destruction and deformities. 2,10 The presence of tophi in gout patients increases with the length of the disease course. 2,10,13 On average, tophi develop 11 years after the initial gout flare-up. 2 While gout tophi are prevalent among 12% to 55% of untreated gout patients overall, older adults with gout are of particular interest. Tophi is more common among older adults with gout and tends to develop relatively earlier in the course of their disease. 14-16 Diagnosis of gout among older adults is also more complicated than among other patients because of the resemblance of gout to rheumatic arthritis and osteoarthritis. 14,16 Equally challenging is the achievement of 2 goals in gout treatment: immediate control of symptoms during the acute phase and maintenance of a low serum uric acid (UA) level (< 6 mg per dL), 10,13 because of existing comorbidities, increased toxicity of medications, and drug interactions in older adults. [14][15][16] The latter goal is especially critical in gout treatment because it may prevent recurrent gout flares, inflammatory responses due to deposition of monosodium urate crystals in joints and soft tissues. Serum UA control may even reverse urate deposition and reduce the complications in the urinary system. 2,10,[17][18][19]20 This study focuses on the economic costs of gout among elderly adults aged 65 years and older and has 3 main objectives. The first objective is to examine health care utilization and direct health care costs among elderly gout patients from a third-party payer's perspective. The existing literature has not provided a comprehensive picture of the economic aspects of gout among older adults, and this research fills this void. The second objective of the study is to analyze direct health care costs among elderly gout patients with tophi, an understudied group. The third objective is to examine the association between serum UA levels and utilization and direct health care costs. While the positive relationship between serum UA and gout is well recognized, epidemiological studies have not focused on the relationship between serum UA and cost.

Data Source
Data in this study were obtained from the Integrated Healthcare Information Services (IHCIS) claims database (1999)(2000)(2001)(2002)(2003)(2004)(2005). IHCIS includes approximately 13 million enrollees (during 2004) from 40 health plans from all census regions in the United States. About 4% of enrollees in the database's commercial or managed care plans are aged 65 years or older. The database contains information on eligibility, medical claims, and pharmacy claims. Inpatient claims are summarized at the stay level. Medical services costs and pharmacy costs are defined as the total allowed After controlling for comorbidities, 12-month all-cause health care cost was $3,038 (33.0%) higher for elderly gout patients than for gout-free members. • Of the $876 total 12-month gout-related costs, 57.6% was attributed to inpatient services, 23.6% to outpatient services, 2.4% to emergency services, 9.4% to other services, and 7.1% to prescription drug costs. • Elderly gout patients with possible tophi incurred higher regression-adjusted total 12-month all-cause health care costs and gout-related costs than those without tophi, with differences of $5,501 and $1,710, respectively. • A very high serum UA level (i.e., ≥ 9 mg per dL) was associated with an additional $3,103 in regression-adjusted total 12-month all-cause health care costs and $276 in regression-adjusted 12-month gout-related costs, compared with a low serum UA level (i.e., < 6 mg per dL).

What this study adds
amount, including the amount paid to the provider plus member cost sharing (e.g., deductible, copayment). Laboratory results are available for some health plans.

Study Sample for Utilization and Cost Analysis of Gout
Enrollees included in this study had a minimum of 1 year continuous eligibility in a health plan both before and after the study index date, defined as the date of the first observed gout diagnosis during the study measurement period from 1999 to 2005 ( Figure 1). Study patients were at least 65 years old on the study index date and had either (1) 2 gout (International Classification of Diseases, Ninth Revision, Clinical Modification, 21 ICD-9-CM, 274.xx) diagnoses that were identified on different dates in the primary or secondary diagnosis code fields or (2) a gout diagnosis and a gout-related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or sulfinpyrazone) identified by National Drug Code (NDC) numbers during the study measurement period. To estimate the medical and pharmacy costs associated with gout, a gout-free comparison sample was selected from the same database using a 1 : 1 match with gout patients, based on age (with a maximum of 1-year difference), gender, and region. Individuals in the comparison group also had 1 year continuous eligibility both before and after the study index date, defined as the same index date as the respective matched gout patient. Moreover, we also identified a subgroup of tophaceous gout patients within the selected sample of gout patients. Gout patients with tophi were defined as those who had an ICD-9-CM code of 274.8x (274.81 = gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear; 274.89 = gout with other specified manifestations) during the 12-month period following the index date. The "other specified manifestations" code was included in our tophi definition because of uncertainty about the accuracy of the 5th digit of the diagnostic codes for tophi in our database.

Study Sample for Utilization and Cost Analysis of Gout by Serum UA Level
The subanalysis of cost by serum UA level focused on patients who had at least 1 serum UA measure in addition to the criteria above. The index date for a patient in this study sample (serum UA index date) was defined as the earliest serum UA lab test date since January 1, 2000. To be included in the serum UA analysis, patients were required to have 1 year of continuous eligibility both before and after the serum UA index date. Utilization and costs for patients in the serum UA subanalysis were examined in the 12-month period following the serum UA index date.

Patient Characteristics
Demographic characteristics (i.e., age, gender, geographic region), comorbidities indicated by the Deyo-Charlson Comorbidity Index (CCI), 22 and the number of unique medications (identified by the first 9 digits of the NDC number in the pharmacy claim) filled during the 12 months before the study index date were included in the analysis. Patients with serum UA data were classified into 3 groups based on serum UA on the serum UA index date: < 6 mg per dL, 6-8.99 mg per dL, and ≥ 9 mg per dL. The cutoff points were chosen based on the relevant literature. The 6 mg per dL mark is the recommended optimal serum UA level. 17,19 The serum UA mark of 9 mg per dL was chosen because the annual incidence of gouty arthritis is much higher beyond this level, compared with a lower serum UA level (4.9% vs. 0.1-0.5%). 23

Utilization and Economic Outcomes
The outcomes in this study included health care utilization and health care costs, which were obtained from the claims database. Health care utilization was measured by the percentage of patients who had any use of inpatient, outpatient and emergency services, and any use of prescription drugs. Each of the medical claims was classified into inpatient, outpatient, emergency, and other services using the place of service field on the claim. Goutrelated medications (i.e., allopurinol, probenecid, colchicines, probenecid/colchicines, and sulfinpyrazone) in the pharmacy claims were identified by NDC number.
Health care costs were estimated from a third-party payer's perspective using both medical and pharmacy claims data during the 12-month period following the study index date for the sample of gout patients and tophaceous gout patients and during the 12-month period following the serum UA index date for the sample with serum UA measures. Two cost categories were assessed in the analysis: total all-cause health care costs and gout-related costs. Both measures included medical services and pharmacy costs. Medical services consisted of inpatient, outpatient, and emergency room (ER) visits, and services provided in other locations. Total all-cause health care costs included costs from medical services and pharmacy claims for any reason. Goutrelated costs included costs from medical services claims with an associated primary or secondary diagnosis of gout and pharmacy claims for gout-related medications (i.e., allopurinol, probenecid, colchicines, or sulfinpyrazone). All costs were inflation adjusted to 2005 dollars using the medical component of the Consumer Price Index.

Statistical Analysis
Health care utilization differences between gout patients and their matched gout-free members were measured as relative risks. Because the matched sample design required statistical tests for paired samples and the skewed utilization data required nonparametric tests, Wilcoxon signed rank sum tests were used to determine statistical significance for continuous variables, and McNemar's tests were used for categorical variables.
Cost differences between gout patients and gout-free members were calculated using both descriptive analysis and multivariate regression. The descriptive analysis estimated the unadjusted differences in the mean per-member 12-month health care costs between gout patients and gout-free members, with statistical significance determined using the Wilcoxon signed rank sum test. The regression was based on a 2-step method adjusting for selected baseline factors, including age at index year, gender, index year, region, CCI, and the number of unique medications filled during the 1-year period before the study index date. The first step in the regression analysis consisted of a 2-part model estimated using the sample of gout-free members. The first part of the 2-part model was a logistic regression model predicting whether any costs were incurred, and the second part was a generalized linear model (GLM) with log link function and gamma distribution to determine the cost amount. These 2 parts generated the predictive models for total all-cause health care costs among the gout-free comparison sample. In the second step, the coefficients from the predictive model were used to estimate the cost of each gout patient as if the patient had been gout-free. The difference between the observed costs and these projected costs was the estimated adjusted cost difference between gout patients and gout-free members. Bootstrap resampling methods were used to estimate the 95% confidence intervals of the health care cost differences. A similar approach was applied to estimate the total all-cause health care cost difference between gout patients with and without possible tophi.
To examine the association between serum UA and utilization and costs of gout patients, we first estimated health care utili- zation and costs for patients in each serum UA category using descriptive statistics. Differences across serum UA categories were assessed for statistical significance using the Pearson chi-square test and the Kruskal-Wallis test, a non-parametric alternative to analysis of variance. Multivariate logistic regressions were then performed to assess the relationship between serum UA levels and risk of all-cause inpatient and ER use, controlling for other patient characteristics including age at index year, gender, index year, region, CCI, and the number of unique medications filled during the 1-year period before the index date. The 2-step regression method described previously was used to assess the association between serum UA levels and health care costs.

Disease-Related and All-Cause Health Care Costs of Elderly Patients With Gout
Predictive accuracy of the logistic regression models was assessed using the c-statistic. Goodness-of-fit for the GLM analyses was assessed using deviance. An a priori 2-tailed α level of 0.05 was used for all statistical tests. All analyses were performed using SAS software, version 9.1 (SAS Institute, Cary, NC).

■■ Results Sample Characteristics
A total of 11,935 pairs of matched gout patients and gout-free comparison members were included in the analysis (Figure 1). The average age of gout patients was 71.4 years (standard deviation [SD] = 4.5, Table 1). The sample was predominantly male (73.5%), reflecting the fact that gout prevalence is higher among men than women. The mean CCI score for the gout patient group was 1.3 (SD = 1.7), which was significantly higher than the comparison group's score (mean = 1.1, SD = 1.6, P < 0.001, Table 1). The mean number of medications filled during the 12-month period before the index date was 9.1 (SD = 7.0) in the gout group and 6.0 (SD = 5.6) in the gout-free group (P < 0.001).
A subgroup of 2,237 gout patients (18.7% of the gout sample) with data on lab values was included in the serum UA analysis. The age and gender distributions for this sub-sample were similar to the distributions for the sample overall (Table 2). However,   Table 2). Most of the patients' characteristics were comparable across the 3 serum UA categories although the group with the highest serum UA level (≥ 9 mg per dL) had a significantly higher prevalence of hypertension and renal impairment compared with the other 2 groups. The gout patients in this group also had a significantly higher CCI score than the other 2 groups (mean = 1.4 vs. 1.0, P = 0.002, Table 2).

Total All-Cause and Gout-Related Utilization and Cost
Nearly all elderly adult gout patients in our sample (99.4%) had at least 1 outpatient visit during the 12 months following the study index date; 29.0% had ≥ 1 claim with an ER place of service, and 27.2% had ≥ 1 claim with an inpatient place of service, and 92.5% had at least 1 pharmacy claim (Table 3). Gout patients had consistently higher utilization in each category than gout-free members. Gout patients were 59.1% more likely to have ≥ 1 claim with an inpatient place of service, and were 50.3% more likely to have ≥ 1 claim with an ER place of service, compared with gout-free members (both P < 0.001). Gout patients also had a higher utilization of out patient services and prescription drugs compared with gout-free members (both risk ratios [RRs] = 1.1; both P < 0.001) although the differences were smaller than those for inpatient and emergency care (RR = 1.6 and 1.5, respectively; P < 0.001). The percentages of patients with gout-related claims with inpatient place of service and ER place of service were 7.4% and 4.8%, respectively. Gout-related outpatient care and prescription drug use occurred in 68.8% and 68.9% of gout patients, respectively (Table 3). In the 12 months following the index date, the mean unadjusted gout-related health care cost per patient was $876 (SD $3,373), 5.9% of the total all-cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted mean total 12-month all-cause health care cost for gout-free members was $9,219 (SD $20,186, Table 3). The unadjusted all-cause health care cost difference between gout patients and gout-free members was $5,515. Of the $876 total 12-month gout-related costs among gout patients, 57.6% was attributed to inpatient services, 23.6% to outpatient services, 2.4% to emergency services, 9.4% to other services, and 7.1% to prescription drug costs.
After statistical adjustment for age at index year, gender, index year, region, CCI, and number of unique medications at baseline, the difference in total 12-month all-cause health care costs between gout patients and members without gout was $3,038 (SE $371, P < 0.001, Figure 2). Among the older adult gout patients included in our sample, 240 (2.0%) had a diagnosis suggesting possible tophi within the 12-month study period. Of these 240 patients, 6.4% had an ICD-9-CM code of 274.8 (a non-specific code for gout with other specified manifestations), 3.9% had an ICD-9-CM of 274.81 (gouty tophi of ear), 43.8% had an ICD-9-CM of 274.82 (gouty tophi of other sites except ear), and 45.8% had an ICD-9-CM of 274.89 (gout with other specified manifestations). Compared to those without tophi, gout patients with possible tophi incurred higher costs in every utilization category. Prior to statistical adjust-ment, total 12-month all-cause health care costs for gout patients with and without tophi were $22,562 (95% CI, $17,182-$27,941) and $14,574 (95% CI, $14,085-$15,063), respectively, a difference of $7,988 (P < 0.001, Figure 3). After adjustment, the difference in 12-month all-cause cost between patients with and without possible tophi was $5,501 (SE $2,626, P < 0.001). The difference in total adjusted 12-month gout-related costs between patients with and without possible tophi was $1,710 (SE $490, P < 0.001, data not shown).

Utilization and Costs by Serum UA Level
Serum UA level was positively associated with all-cause hospitalization and ER visits ( Table 4). Patients in the highest serum UA category (≥ 9 mg per dL) were more likely to have ≥ 1 claim with an inpatient place of service (33.2%) during the 12-month period following the serum UA index date than were patients with a serum UA value < 6 mg per dL (24.0%, P = 0.012). These patients also had a higher use of ER services compared with patients with a serum UA < 6 mg per dL (29.5% versus 23.1%, P = 0.035). Outpatient utilization and use of prescription drugs were similar across serum UA levels (Table 4).
Logistic regression analysis, which controlled for age at index year, gender, index year, region, CCI, and the number of unique medications during the 1-year period before the index serum UA date, revealed that the odds ratio of having an inpatient place of service claim among patients with a serum UA ≥ 9mg per dL was 1.4 (95% CI, 1.1-1.9) compared with patients with a serum UA < 6 mg per dL. The c-statistic for the hospitalization regression model was 0.643.
Health care costs were also positively associated with serum UA level. Among all patients with a serum UA value, mean unadjusted 12-month all-cause total health care costs were $15,025 (SD = $29,348) during the 12-month study period. Adjusted total all-cause health care costs for patients with a serum UA ≥ 9 mg per dL were $18,340, $3,103 higher than costs for those with a serum UA < 6 mg per dL (P = 0.02, Figure 4). Adjusted total all-cause health care costs for patients with a serum UA of 6-8.99 mg per dL ($14,935) and patients with a serum UA < 6 mg per dL ($15,237) were not significantly different.
Gout-related utilization was also positively associated with a higher serum UA level, except for use of prescription drugs. The percentages of members with ≥ 1 gout-related claim with an inpatient place of service were 2.1% in the group with serum UA < 6mg per dL, 3.6% among those with serum UA between 6 and 8.99 mg per dL, and 9.3% among those with serum UA ≥ 9 mg per dL (P < 0.001). Mean unadjusted 12-month gout-related costs among all patients with a serum UA value were $481 (SD = $2,256). Adjusted gout-related health care costs among patients with a serum UA ≥ 9 mg per dL were $723, $276 higher than costs for patients with a serum UA < 6 mg per dL (P < 0.001, Figure 4). Adjusted gout-related costs for patients with a serum UA of 6-8.99 mg per dL ($408) and patients with a serum UA < 6 mg per dL ($447) were not significantly different. Among patients with low, moderate-high, and very high serum UA levels, regression-adjusted gout-related costs represented 2.9%, 2.7%, and 3.9% of total regression-adjusted health care costs, respectively.

■■ Discussion
This study employed a nation wide claims database to examine health care utilization and health care costs associated with gout from a third-party payer's perspective. The analysis focused on  the older adult population, in which a higher prevalence of the disease is observed. In addition, the study also compared health costs between gout patients with and without tophi and across different serum UA categories. This study adds to a limited literature on health care utilization and costs among older adult gout patients.
The findings in this study demonstrated that older adult gout patients incur substantially higher total all-cause health care costs than older adult gout-free members, $5,515 higher in a 12-month period. This number represents the total health care cost associated with gout: how much more a third-party payer has to pay for an average gout patient compared with an average gout-free member, irrespective of the associated comorbidities. 24 After statistical adjustments for the comorbidities measured in our study and the number of medications, the 12-month all-cause cost difference between gout patients and gout-free members was $3,038.
The mean gout-related costs in this sample were estimated to be $876 for a 12-month period, about 5.9% of total health care costs. Of the $876, 57.6% was attributed to inpatient services, 23.6% to outpatient services, 2.4% to emergency services, 9.4% to other services, and 7.1% to prescription drug costs.
Gout patients with possible tophi incurred significantly higher regression-adjusted total all-cause health care costs and goutrelated costs than those without tophi, with differences of $5,501 and $1,710 respectively. The occurrence of tophi represents a more advanced stage of gout, which generally requires more medical resources than the initial self-limiting stage. For example, renal complications, such as chronic urate nephropathy, occur more often in tophaceous gout. 2 Previous research also found that tophi are associated with more frequent gout flares. 17 Therefore, it is not surprising that gout patients with tophi have considerably higher total health care costs and gout-related costs.
Finally, the study documented a positive relationship between serum UA and health care utilization and costs among gout patients. The prevalence of use of services in an inpatient place of service was significantly higher among patients with serum UA ≥ 9 mg per dL than among patients with low serum UA (< 6 mg per dL). Moreover, serum UA ≥ 9 mg per dL was associated with higher total all-cause health care costs and gout-related health care costs. Having serum UA ≥ 9 mg per dL was associated with an additional $3,103 in 12-month all-cause health care costs and $276 in 12-month gout-related costs, compared with a serum UA < 6 mg per dL.
Although gout is a prevalent disease associated with substantial utilization of health care resources, the economic burden of gout has not been well documented. Kim 12 The cost differences between gout patients and non-gout members in our study were much higher than in previous work. This is probably because our study focused on older adults. Older gout patients constitute a difficult population in gout treatment because of the high prevalence of complications and comorbidities in this group. In addition, impaired renal function, increased drug toxicity, and multiple drug interactions pose further barriers to effective control of hyperuricemia in this group. 18,19 These facts suggest that older adult gout patients may consume more health care resources than their younger counterparts.
The goal of maintaining the optimal serum UA (≤ 6 mg per dL) is extremely challenging in the older adult population. Behavioral changes alone, such as restricting diet, reducing alcohol consumption, and switching incorrect medications, generally produce unsatisfactory results. 16 In such cases, urate-lowering drugs are usually recommended by physicians. Currently, there are 2 types of urate-lowering drugs: uricosuric drugs (e.g., probenecid, sulfinpyrazone) and hypouricemic drugs (e.g., allopurinol). While effective in reducing serum UA in most patients, the use of uricosuric drugs is limited in some older adults because of decline in renal function; according to gout treatment guidelines published in 1999, uricosuric drugs should not be given to patients with a urine output of < 1 mL per minute, a creatinine clearance of < 50 mL per minute (0.84 mL per second) or a history of renal calculi. 25 Allopurinol is the most commonly prescribed urate-lowering drug and is the drug of choice for this purpose in patients with renal impairment. 16 Allopurinol is generally well tolerated, but approximately 2% of patients develop a pruritic, erythematous rash that requires discontinuation of therapy, and 0.4% of patients experience allopurionol hypersensitivity syndrome. 10 However, both of these adverse effects may be minimized by keeping the allopurinol dose low in aged patients or those with renal impairment, with a starting dose of 50 mg-100 mg on alternate days, to a maximum daily dose of about 100 mg-300 mg, based upon the patient's creatinine clearance and serum urate level. 10,16 Additional treatment options to lower serum urate would be welcomed, especially those with improved effectiveness and fewer side effects. Future studies on medication use and its association with other health care utilization may shed more light on the economic aspects of gout treatment.

Limitations
First, the adjusted difference in total all-cause health care costs between gout patients and gout-free members is subject to bias because of potential confounders. The gout patients and gout-free members in our sample had different comorbidities based on the CCI. Although we controlled for the CCI in our model, there may be residual confounding, such as disease severity, that affects our estimation of the excess cost of gout. However, the unadjusted difference, which represents the additional cost associated with gout, is still valid for the purpose of estimating how much more a gout patient costs relative to a gout-free member, although the majority of the cost difference could be due to comorbidities. 24 Second, because the study was observational, it was unable to identify a causal relationship between gout and excess all-cause health care costs. Third, though the analysis was conducted to include allowed amounts for costs, which includes not only third-party payer payment but also patient cost sharing, the indirect costs that might be incurred by patients and their caregivers were not included.
Fourth, as a general limitation with the use of a claims database, costs may not be accurately classified as gout-related or tophi-related because the calculation was based only on the listed diagnoses in the claims. Moreover, when estimating prescription drug costs, we included only allopurinol, probenecid, colchicines, probenecid/colchicines, and sulfinpyrazone as goutrelated drugs. We excluded non-steroidal inflammatory drugs (NSAIDs), a common medication used in acute gouty arthritis, because this class of drug is non-specific and is commonly prescribed for other non-gout related conditions. Additionally, most NSAIDs are over-the-counter drugs, the use of which is not possible to capture using claims data. Fifth, we based our medical service classifications only on place of service codes instead of more specific revenue and procedure codes. To the extent that ER room and outpatient services were coded with inpatient place of service, our inpatient cost estimates were inflated. This may be an issue for the serum UA analysis, in particular, if those in the highest category receive certain types of outpatient treatment (e.g., dialysis) that are more likely than other serum UA categories to be coded with inpatient place of service. That said, this potential problem about place of service would not affect comparisons of total cost across the study groups.
Sixth, the serum UA analysis measured costs for the 12 months following the earliest serum UA test in the database. Because we did not measure the degree to which the 12-month serum UA analysis time period coincided with the 12-month analysis period for gout-related costs, it is possible that these 2 analyses measured costs incurred in different time periods.
A seventh limitation arises from the way that gout patients with tophi were defined. The tophi-related classification was based on the 4-digit ICD-9-CM code of 274.8x. The 5-digit classification code of 274.89, however, is "gout with other specified manifestations," which may or may not represent tophi. Of the 240 patients that we identified as having tophi, 45.8% had an ICD-9-CM code 274.89. We chose to identify tophi using 4-digit rather than 5-digit codes because of concerns about the accuracy of 5-digit codes in our database. Some gout tophi patients in our sample may, therefore, be misclassified as a result of relying on ICD-9-CM codes at the 4-digit level.
Other limitations are specific to the analysis of a sub-sample of gout patients with a serum UA value. Most gout patients with a valid serum UA value from electronic laboratory data were concentrated in the mid-and south-Atlantic region, which resulted in a study sample not representative of all geographic locations. In addition, compared with the overall sample of older adult gout patients in this study (including patients both with and without a serum UA lab test), gout patients with a serum UA lab value seem to have fewer comorbidities indicated by the CCI (mean of 1.1 vs. 1.3). However, the differences were small, so the results may not significantly deviate from the findings that we would have obtained if all gout patients were included.

■■ Conclusions
Gout-related costs represent approximately 6% of total health care costs in elderly patients with gout. Gout is associated with increased health care utilization and costs among elderly adults. Patients with possible tophi, in particular, had increased health care costs. Gout patients with a serum UA ≥ 9 mg per dL incur higher costs than those with a serum UA < 6 mg per dL.